The purpose of the proposed program is to bring additional basic immunochemical, biochemical, and cell biology techniques to bear on the clinical problems of rheumatic disease and to continue existing clinical and pathophysiologic investigative programs. Studies on the chemical mediators of tissue injury continue to focus on the development of immunochemical methods for the measurement of the kinin system, the fibrinolytic sequence, and certain aspects of the clotting system, and the application of this methodology to determining the roles of these systems in rheumatic inflammation. Other studies include the measurement of the individual components of the classical and alternative complement sequences in serum and synovial fluid in an attempt to determine the mechanism for the intra-articular activation of this sequence in the rheumatoid joint. Effector molecules released from one cell, such as the mast cell, polymorphonuclear leukocyte, and lymphocyte, and acting to alter the function of other cells are being analyzed with the concomitant development of clinical assays. In vitro methods have been applied to the study of cellular immunity in humans and are being used to assess the possible contributions of this reaction mechanism to various disease states. Investigations of the serologic abnormalities have revealed inherited abnormalities of complement in relation to genetic markers, and this lead is being actively pursued.